title: Human candidate polymorphisms in sympatric ethnic groups differing in malaria susceptibility in Mali.
abstract: Malaria still remains a major public health problem in Mali, although disease susceptibility varies between ethnic groups, particularly between the Fulani and Dogon. These two sympatric groups share similar socio-cultural factors and malaria transmission rates, but Fulani individuals tend to show significantly higher spleen enlargement scores, lower parasite prevalence, and seem less affected by the disease than their Dogon neighbours. We have used genetic polymorphisms from malaria-associated genes to investigate associations with various malaria metrics between the Fulanai and Dogon groups. Two cross sectional surveys (transmission season 2006, dry season 2007) were performed. Healthy volunteers from the both ethnic groups (n=939) were recruited in a rural setting. In each survey, clinical (spleen enlargement, axillary temperature, weight) and parasitological data (malaria parasite densities and species) were collected, as well as blood samples. One hundred and sixty six SNPs were genotyped and 5 immunoassays (AMA1, CSP, MSP1, MSP2, total IgE) were performed on the DNA and serum samples respectively. The data confirm the reduced malaria susceptibility in the Fulani, with a higher level of the protective O-blood group, and increased circulating antibody levels to several malaria antigens (p<10(-15)). We identified SNP allele frequency differences between the 2 ethnic groups in CD36, IL4, RTN3 and ADCY9. Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and IL13 genes were correlated with antibody production (p-value<0.003). Further work is required to understand the mechanisms underpinning these genetic factors.
authors.affiliation: Malaria Research and Training Center / Department of Epidemiology of Parasitic Diseases / Faculty of Medicine, Pharmacy and Odonto - Stomatology, BP 1805, Bamako, USTTB, Mali ; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Bakary
authors.initials: B
authors.lastname: Maiga
authors.forename: Amagana
authors.initials: A
authors.lastname: Dolo
authors.forename: Ousmane
authors.initials: O
authors.lastname: Touré
authors.forename: Victor
authors.initials: V
authors.lastname: Dara
authors.forename: Amadou
authors.initials: A
authors.lastname: Tapily
authors.forename: Susana
authors.initials: S
authors.lastname: Campino
authors.forename: Nuno
authors.initials: N
authors.lastname: Sepulveda
authors.forename: Paul
authors.initials: P
authors.lastname: Risley
authors.forename: Nilupa
authors.initials: N
authors.lastname: Silva
authors.forename: Nipula
authors.initials: N
authors.lastname: Silva
authors.forename: Patrick
authors.initials: P
authors.lastname: Corran
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.forename: Dominic
authors.initials: D
authors.lastname: Kwiatkowski
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
authors.forename: Marita
authors.initials: M
authors.lastname: Troye-Blomberg
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D060467:Disease Resistance / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000208:ethnology* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008302:Mali / Q000208:ethnology; D010641:Phenotype; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D061350:Sympatry
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines